The autosomal recessive ob gene is expressed in homzygous mice (C57BL/6J ob/ob, Bar Harbor, ME) by a number of endocrine and metabolic abnormalities similar in many respects to those displayed by many human maturity-onset diabetics. The similarities include obesity, fasting hyperglycemia, elevated insulin levels, glucose intolerance and resistance to exogenous insulin. In the present proposal, we outline a series of studies to examine a) the sequential development in the perinatal period of the metabolic and endocrine disturbances associated with mice having ob/ob or ob/plus genotypes; b) the contribution of the quantity and quality of food intake in the pre- and post-weaning periods to the development of the abnormalities; and c) the possible contribution of early hyperinsulinemia and hyperadrenocorticoidism to the manifestation of the metabolic disturbances displayed by these animals.